Mammalian cell size variation as growth rate varies. Panel (a) shows a given mammalian cell growing at different rates and with different sizes. The lines are parallel because the interdivision times are normalized to a relative cell age as cells are born at age 0.0 and divide at age 1.0. All lines are exponentially increasing cell sizes from smallest to largest. Where the lines cross the thick horizontal line indicates a cell of size 1.0. Since the fastest cell (cell g) has a size 1.0 at the start of the cell cycle these cells must go from a newborn sizes of 1.0 to a size at division of 2.0. The slowest cell (cell a) has size 1.0 toward the end of the cell cycle, so the newborn cell is slightly larger than size 0.5 at age 0.0. The size ranges of these cells goes over a factor of 2. In panel (b) the size patterns are re-interpreted in terms of initiation at a particular time during the cell cycle. In this figure the thick, short line on each pattern is the S phase, the thinner line to the right is the G2 phase and the thinner line to the left is the G1 phase. Given that S and G2 are relatively constant in length then the slower cells (e.g., cell "a") have a longer G1 phase than the faster growing cells (e.g., cell "g", which has no measurable G1 phase). This is because the interdivision time is the sum of S+G2+G1. If S and G2 are relatively constant as the interdivision time decreases (i.e., as cells grow at faster growth rates), the G1 phase gets smaller. When the interdivision time equals the sum of S and G2 as in cell "g", there is no G1 phase. Such a situation has been analyzed previously (Cooper, 1979). It is clear from panel (b) that as cells grow faster, the time during the division cycle at which initiation of S phase starts is earlier and earlier. This is illustrated even more directly in panel (c) where the phases are normalized to a unit length. The slowest cell (cell "a") has the shortest fraction of cells with an S or G2 phase and the fastest growing cell (cell "g") has the entire division cycle occupied by S and G2 phases. The topmost line in panel (c) is the fastest cell and it starts S phase early in the cell cycle. Thus we see that the faster a cell grows the earlier in the cell cycle the cell achieves a size of 1.0. This accounts for the result that the slower cell has a smaller cell size than the faster growing cell.